1. Field of the Invention
The present invention is broadly concerned with an improved method and vaccine for the immunization of swine against infectious diseases caused by bacteria which secrete RTX toxins, such as pleuropneumonia, pneumonia, enteritis, septicemia and rhinitis sore particularly, the invention pertains to such a method and vaccine which includes an effective amount of a live, immunizing, RTX toxin-secreting organism which induces in the swine a sufficiently high RTX toxin-neutralizing antibody titer to at least prevent clinical symptoms of the diseases.
2. Description of the Prior Art
A number of gram-negative bacteria are known to secrete RTX toxins in swine. Such bacteria are generally selected from the group consisting of the genera Actinobacillus, Pasteurella, Haemophilus, Escherichia and Salmonella. The RTX toxins are a family of calcium-dependent, pore-forming, secreted toxins.
Organisms which secrete RTX toxins are known to cause a variety of debilitating swine diseases such as pleuropneumoniae pneumonia, enteritise septicemia and rhinitis. These diseases, and particularly porcine pleuropneumonia, have very serious economic consequences for pig farmers. Susceptible pigs exposed to aerosolized A. pleuropneumoniae develop acute necrotic bronchopneumonia following inhalation of a threshold number of organisms. The toxins produced by A. pleuropneumoniae and the associated inflammatory response rapidly induce focal vascular necrosis leading to localized thrombosis, edema, ischemic necrosis, and fibrinous pleuritis. The severity of the diseases following exposure to A. pleuropneumoniae is dependent on the relative virulence of the strain involved and the number of organisms inhaled. In a typical pleuropneumonia outbreak caused by a virulent strain of A. pleuropneumoniae, morbidity may be in excess of 50% with mortality being quite variable, from 1-10%. Growing pigs are often most severely affected, although immunologically susceptible sows, boars and piglets may also develop severe disease. A full discussion of the causes, epidemiology and treatment of pleuropneumonia is set forth in Fenwick et al., Porcine Pleuropneumonia: An Update, J. Am. Vet. Ned. Assoc., 1994; 204:334, which is incorporated by reference herein.
While the impact of porcine pleuropneumonia and other diseases caused by bacteria which secrete RTX toxins is well known, there have heretofore been no commercially available vaccines with the ability to reliably induce protective immunity against these diseases. Some vaccines reduce mortality rates, but none are effective in preventing infections of A. pleuropneumoniae or apparently the development of carrier pigs capable of shedding the organism. Additionally, difficulties with antigens and adjuvants have led to injection site lesions. As far as is known, none of the prior vaccines induce significant neutralizing antibody titers in swine against the exotoxins such as the RTX toxins secreted by the etiologic organisms.
There is accordingly a real and unsatisfied need in the art for an improved vaccine and method whereby swine may be immunized against infectious diseases caused by bacteria which secrete RTX toxins.